The overall objective of this research is to contribute to our fundamental knowledge of pathogenesis and immunologic responses of diseased hosts. The overall objective of this proposed research is to develop means to prevent and treat primary amebic meningoencephalitis of man due to Naegleria fowleri. The current proposal directly addresses the role of host resistance and virulence factors in the pathogenesis of naeglerial infections. These proposed studies on host resistance in mice to naeglerial infections and the factors that influence virulence will provide a scientific basis for developing means to prevent and treat primary amebic meningoencephalitis in man. The specific aims of this project are as follow: (a) to determine which factors affect the virulence of N. fowleri for mice (culture conditions; products of N. fowleri that contribute to invasiveness and toxicity); (b) to define the natural host resistance factors that limit naeglerial infections in the laboratory mouse; for example, immunocompetence; (c) to develop procedures for immunizing mice against fatal disease; and (d) to determine the immunologic bases for acquired immunity to N. fowleri infections.